Decreased Brain pH as a Shared Endophenotype of Psychiatric Disorders

Hideo Hagihara, Vibeke S. Catts, Yuta Katayama, Hirotaka Shoji, Tsuyoshi Takagi, Freesia L. Huang, Akito Nakao, Yasuo Mori, Kuo Ping Huang, Shunsuke Ishii, Isabella A. Graef, Keiichi I. Nakayama, Cynthia Shannon Weickert, Tsuyoshi Miyakawa

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Although the brains of patients with schizophrenia and bipolar disorder exhibit decreased brain pH relative to those of healthy controls upon postmortem examination, it remains controversial whether this finding reflects a primary feature of the diseases or is a result of confounding factors such as medication and agonal state. To date, systematic investigation of brain pH has not been undertaken using animal models that can be studied without confounds inherent in human studies. In the present study, we first reevaluated the pH of the postmortem brains of patients with schizophrenia and bipolar disorder by conducting a meta-analysis of existing data sets from 10 studies. We then measured pH, lactate levels, and related metabolite levels in brain homogenates from five neurodevelopmental mouse models of psychiatric disorders, including schizophrenia, bipolar disorder, and autism spectrum disorder. All mice were drug naive with the same agonal state, postmortem interval, and age within each strain. Our meta-analysis revealed that brain pH was significantly lower in patients with schizophrenia and bipolar disorder than in control participants, even when a few potential confounding factors (postmortem interval, age, and history of antipsychotic use) were considered. In animal experiments, we observed significantly lower pH and higher lactate levels in the brains of model mice relative to controls, as well as a significant negative correlation between pH and lactate levels. Our findings suggest that lower pH associated with increased lactate levels is not a mere artifact, but rather implicated in the underlying pathophysiology of schizophrenia and bipolar disorder.

Original languageEnglish
Pages (from-to)459-468
Number of pages10
JournalNeuropsychopharmacology
Volume43
Issue number3
DOIs
Publication statusPublished - Feb 1 2018

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Endophenotypes
Psychiatry
Bipolar Disorder
Brain
Schizophrenia
Lactic Acid
Meta-Analysis
Artifacts
Antipsychotic Agents
Autopsy
Animal Models

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Hagihara, H., Catts, V. S., Katayama, Y., Shoji, H., Takagi, T., Huang, F. L., ... Miyakawa, T. (2018). Decreased Brain pH as a Shared Endophenotype of Psychiatric Disorders. Neuropsychopharmacology, 43(3), 459-468. https://doi.org/10.1038/npp.2017.167

Decreased Brain pH as a Shared Endophenotype of Psychiatric Disorders. / Hagihara, Hideo; Catts, Vibeke S.; Katayama, Yuta; Shoji, Hirotaka; Takagi, Tsuyoshi; Huang, Freesia L.; Nakao, Akito; Mori, Yasuo; Huang, Kuo Ping; Ishii, Shunsuke; Graef, Isabella A.; Nakayama, Keiichi I.; Shannon Weickert, Cynthia; Miyakawa, Tsuyoshi.

In: Neuropsychopharmacology, Vol. 43, No. 3, 01.02.2018, p. 459-468.

Research output: Contribution to journalArticle

Hagihara, H, Catts, VS, Katayama, Y, Shoji, H, Takagi, T, Huang, FL, Nakao, A, Mori, Y, Huang, KP, Ishii, S, Graef, IA, Nakayama, KI, Shannon Weickert, C & Miyakawa, T 2018, 'Decreased Brain pH as a Shared Endophenotype of Psychiatric Disorders', Neuropsychopharmacology, vol. 43, no. 3, pp. 459-468. https://doi.org/10.1038/npp.2017.167
Hagihara, Hideo ; Catts, Vibeke S. ; Katayama, Yuta ; Shoji, Hirotaka ; Takagi, Tsuyoshi ; Huang, Freesia L. ; Nakao, Akito ; Mori, Yasuo ; Huang, Kuo Ping ; Ishii, Shunsuke ; Graef, Isabella A. ; Nakayama, Keiichi I. ; Shannon Weickert, Cynthia ; Miyakawa, Tsuyoshi. / Decreased Brain pH as a Shared Endophenotype of Psychiatric Disorders. In: Neuropsychopharmacology. 2018 ; Vol. 43, No. 3. pp. 459-468.
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